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Browsing by Author "Unverzagt, Fred"
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Item ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort(American Academy of Neurology, 2014-09-30) Alexander, Kristine S.; Zakai, Neil A.; Gillett, Sarah; McClure, Leslie A.; Wadley, Virginia; Unverzagt, Fred; Cushman, Mary; Department of Medicine, IU School of MedicineOBJECTIVE: To assess the relationships among ABO group, factor VIII (FVIII), and incident cognitive impairment in a large, prospective cohort study of black and white adults in the United States using a nested case-control design. METHODS: Incident cognitive impairment was defined using cognitive domain tests over a mean follow-up of 3.4 years. ABO blood group was measured by genotyping in a nested case-control sample of 495 cases with cognitive impairment and 587 controls. RESULTS: Those with blood group AB and those with higher FVIII had an increased risk of cognitive impairment, adjusting for age, race, region, and sex (respective odds ratios 1.82, 95% confidence interval [CI] 1.15-2.90; and 1.24, 95% CI 1.10-1.38 for 40 IU/dL higher FVIII). Mean FVIII was higher in those with blood type AB (142 IU/dL; 95% CI 119-165) compared with O (104 IU/dL; 95% CI 101-107), and FVIII mediated 18% of the association between AB group and incident cognitive impairment (95% CI for mediation -30% to 68%). CONCLUSIONS: Blood group AB and higher FVIII were associated with increased incidence of cognitive impairment in this prospective study. The association of blood group AB with incident cognitive impairment was not significantly mediated by FVIII levels.Item Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive Impairment in Older Adults in Primary Care(Wiley, 2018) Campbell, Noll L.; Lane, Kathleen A.; Gao, Sujuan; Boustani, Malaz A.; Unverzagt, Fred; Medicine, School of MedicineStudy Objective To determine the influence of anticholinergic medications on transitions in cognitive diagnosis of older adults in primary care. Design This observational cohort study was conducted over a mean follow‐up of 3.2 years. Anticholinergic exposure was defined by pharmacy dispensing and claims records. Cognitive diagnosis was performed by an expert panel at baseline and annually up to 4 years. Data Source Medication exposure and other clinical data were extracted from the Indiana Network for Patient Care (INPC). The cognitive diagnosis was derived from a cognitive screening and diagnosis study. Participants A total of 350 adults 65 years and older without dementia and receiving primary care in a safety net health care system. Measurement and Main Results Cognitive diagnosis followed a two‐phase screening and consensus‐based neuropsychiatric examination to determine a baseline diagnosis as normal cognition, mild cognitive impairment (MCI), or dementia, with a follow‐up neuropsychiatric examination and consensus‐based diagnosis repeated annually. The Anticholinergic Cognitive Burden scale was used to identify anticholinergics dispensed up to 10 years before enrollment and annually throughout the study. A total standard daily dose of anticholinergics was calculated by using pharmacy dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic assessments were completed over a mean follow‐up of 3.2 years. Compared with stable cognition, increasing use of strong anticholinergics calculated by total standard daily dose increased the odds of transition from normal cognition to MCI (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, p = 0.0342). Compared with stable MCI, strong anticholinergics did not influence the reversion of MCI to normal cognition (OR 0.95, 95% CI 0.86–1.05, p = 0.3266). Conclusion De‐prescribing interventions in older adults with normal cognition should test anticholinergics as potentially modifiable risk factors for cognitive impairment.Item Lifecourse socioeconomic position and diabetes incidence in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, 2003 to 2016(Elsevier, 2021-12) Martin, Kimberly D.; Beckles, Gloria L.; Wu, Chengyi; McClure, Leslie A.; Carson, April P.; Bennett, Aleena; Bullard, Kai McKeever; Glymour, Maria; Unverzagt, Fred; Cunningham, Solveig; Imperatore, Giuseppina; Howard, Virginia J.; Psychiatry, School of MedicineLow socioeconomic position (SEP) across the lifecourse is associated with Type 2 diabetes (T2DM). We examined whether these economic disparities differ by race and sex. We included 5448 African American (AA) and white participants aged ≥45 years from the national (United States) REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort without T2DM at baseline (2003–07). Incident T2DM was defined by fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or using T2DM medications at follow-up (2013–16). Derived SEP scores in childhood (CSEP) and adulthood (ASEP) were used to calculate a cumulative (CumSEP) score. Social mobility was defined as change in SEP. We fitted race-stratified logistic regression models to estimate the association between each lifecourse SEP indicator and T2DM, adjusting for covariates; additionally, we tested SEP-sex interactions. Over a median of 9.0 (range 7–14) years of follow-up, T2DM incidence was 167.1 per 1000 persons among AA and 89.9 per 1000 persons among white participants. Low CSEP was associated with T2DM incidence among AA (OR = 1.61; 95%CI 1.05–2.46) but not white (1.06; 0.74–2.33) participants; this was attenuated after adjustment for ASEP. In contrast, low CumSEP was associated with T2DM incidence for both racial groups. T2DM risk was similar for stable low SEP and increased for downward mobility when compared with stable high SEP in both groups, whereas upward mobility increased T2DM risk among AAs only. No differences by sex were observed. Among AAs, low CSEP was not independently associated with T2DM, but CSEP may shape later-life experiences and health risks.Item Randomized double-masked controlled trial of cognitive training in breast cancer survivors: a preliminary study(Springer, 2022) Von Ah, Diane; McDonald, Brenna C.; Crouch, Adele D.; Ofner, Susan; Perkins, Susan; Storey, Susan; Considine, Robert; Unverzagt, Fred; Radiology and Imaging Sciences, School of MedicinePurpose: To evaluate the acceptability, satisfaction, and preliminary efficacy of cognitive training for improving cognitive function and health outcomes in breast cancer survivors (BCS). Patients and methods: BCS enrolled in this 2-group randomized, double-masked controlled trial of cognitive training. Primary outcomes included the acceptability and satisfaction of the interventions. Secondary outcomes included examining the effect size and reliable improvement of perceived cognitive function and health outcomes, including work ability, health perception (status and change), and quality of life. Exploratory outcomes were performance on neuropsychological tests and plasma levels of brain-derived neurotropic factor (BDNF). Data were collected at baseline and immediately post-intervention. Using ANCOVA models, the intervention was compared to attention control while adjusting for covariates and baseline values. The effect sizes for differences in means and the reliable improvement percentage were reported. Results: Thirty-six BCS completed the study and were on average 57.6 (SD = 8.0) years old, 59.4% Caucasian, and had some college education (74.5%). Both programs were reported to be satisfactory and acceptable. Non-significant small effect sizes were noted for the intervention on cognitive abilities (d = 0.26) and cognitive concerns (d = - 0.32), with reliable improvement noted in 32% and 28% of BCS, respectively. Small to medium effect sizes were noted in improvement in work ability (d = 0.37) and health perception status (d = 0.30) and change (d = 0.60, p < 0.05). Conclusions: Cognitive training was acceptable to BCS and resulted in improvement in perceived cognitive function and perceptions of "real-world" health benefits. A larger randomized controlled trial is warranted to determine its effectiveness for objective cognitive performance.Item Relation of Atrial Fibrillation to Cognitive Decline (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study)(Elsevier, 2021) Bailey, Margie J.; Soliman, Elsayed Z.; McClure, Leslie A.; Howard, George; Howard, Virginia J.; Judd, Suzanne E.; Unverzagt, Fred; Wadley, Virginia; Sachs, Bonnie C.; Hughes, Timothy M.; Psychiatry, School of MedicineThe association of atrial fibrillation (AF) with cognitive function remains unclear, especially among racially/geographically diverse populations. This analysis included 25,980 black and white adults, aged 48+, from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, free from cognitive impairment and stroke at baseline. Baseline AF was identified by self-reported medical history or electrocardiogram (ECG). Cognitive testing was conducted yearly with the Six Item Screener (SIS) to define impairment and at 2-year intervals to assess decline on: animal naming and letter fluency, Montreal Cognitive Assessment (MoCA), Word List Learning (WLL) and Delayed Recall tasks (WLD). Multivariable regression models estimated the relationships between AF and baseline impairment and time to cognitive impairment. Models were adjusted sequentially for age, sex, race, geographic region, and education, then cardiovascular risk factors and finally incident stroke. AF was present in 2,168 (8.3%) participants at baseline. AF was associated with poorer baseline performance on measures of: semantic fluency (p<0.01); global cognitive performance (MoCA, p<0.01); and WLD (p<0.01). During a mean follow-up of 8.06 years, steeper declines in list learning were observed among participants with AF (p<0.03) which remained significant after adjusting for cardiovascular risk factors (p<0.04) and incident stroke (p<0.03). Effect modification by race, sex and incident stroke on AF and cognitive decline were also detected. In conclusion, AF was associated with poorer baseline cognitive performance across multiple domains and incident cognitive impairment in this bi-racial cohort. Additional adjustment for cardiovascular risk factors attenuated these relations with the exception of learning.Item Risk factors for the progression of mild cognitive impairment to dementia(Elsevier, 2013-11) Campbell, Noll L.; Unverzagt, Fred; LaMantia, Michael A.; Khan, Babar A.; Boustani, Malaz A.; Psychiatry, School of MedicineThe increasing prevalence of cognitive impairment among the older adult population warrants attention to the identification of practices that may minimize the progression of early forms of cognitive impairment, including the transitional stage of mild cognitive impairment (MCI), to permanent stages of dementia. This article identifies both markers of disease progress and risk factors linked to the progression of MCI to dementia. Potentially modifiable risk factors may offer researchers a point of intervention to modify the effect of the risk factor and to minimize the future burden of dementia.Item Vascular-brain Injury Progression after Stroke (VIPS) Study: concept for understanding racial and geographic determinants of cognitive decline after stroke(Elsevier, 2020) Sarfo, Fred Stephen; Akinyemi, Rufus; Howard, George; Howard, Virginia J.; Wahab, Kolawole; Cushman, Mary; Levine, Deborah A.; Ogunniyi, Adesola; Unverzagt, Fred; Owolabi, Mayowa; Ovbiagele, Bruce; Psychiatry, School of MedicineCognitive impairment and dementia (CID) are major public health problems with substantial personal, social, and financial burdens. African Americans are at a heightened risk for Vascular Cognitive Impairment (VCI) compared to European Americans. Recent lines of evidence also suggest a high burden of Post-stroke VCI among indigenous Africans. A better understanding of the cause(s) of the racial disparity in CID, specifically VCI, is needed in order to develop strategies to reduce it. We propose and discuss the conceptual framework for a unique tri-population, trans-continental study titled The Vascular brain Injury Progression after Stroke (VIPS) study. The overarching objective of the VIPS Study will be to explore the interplay of multiple factors (racial, geographical, vascular, lifestyle, nutritional, psychosocial and inflammatory) influencing the level and trajectory of post-stroke cognitive outcomes and examine whether differences between indigenous Africans, African Americans and European Americans exist. We hypothesize that differences which might be due to racial factors will be observed in African Americans versus European Americans as well as Indigenous Africans versus European Americans but not in African Americans versus Indigenous Americans; differences due to geographical factors will be observed in Indigenous Americans versus African Americans and Indigenous Africans versus European Americans but not in African Americans versus European Americans. This overarching objective could be accomplished by building upon existing National Institutes of Health investments in the REasons for Geographical And Racial Differences in Stroke (REGARDS) study (based in the United States of America) and the Stroke Investigative Research and educational Network (SIREN) study (based in Sub-Saharan Africa).